Electrophysiological Activity Research Articles

ℛSCZ: A Riemannian schizophrenia diagnosis framework based on the multiplexity of EEG-based dynamic functional connectivity patterns

Abnormal electrophysiological (EEG) activity has been largely reported in schizophrenia (SCZ). In the last decade, research has focused to the automatic diagnosis of SCZ via the investigation of an EEG aberrant activity and connectivity linked to this mental disorder. These studies followed various preprocessing steps of EEG activity focusing on frequency-dependent functional connectivity brain network (FCBN) construction disregarding the topological dependency among edges. FCBN belongs to a family of symmetric positive definite (SPD) matrices forming the Riemannian manifold. Due to its unique geometric properties, the whole analysis of FCBN can be performed on the Riemannian geometry of the SPD space. The advantage of the analysis of FCBN on the SPD space is that it takes into account all the pairwise interdependencies as a whole. However, only a few studies have adopted a FCBN analysis on the SPD manifold, while no study exists on the analysis of dynamic FCBN (dFCBN) tailored to SCZ. In the present study, I analyzed two open EEG-SCZ datasets under a Riemannian geometry of SPD matrices for the dFCBN analysis proposing also a multiplexity index that quantifies the associations of multi-frequency brainwave patterns. I adopted a machine learning procedure employing a leave-one-subject-out cross-validation (LOSO-CV) using snapshots of dFCBN from (N-1) subjects to train a battery of classifiers. Each classifier operated in the inter-subject dFCBN distances of sample covariance matrices (SCMs) following a rhythm-dependent decision and a multiplex-dependent one. The proposed ℛSCZ decoder supported both the Riemannian geometry of SPD and the multiplexity index DC reaching an absolute accuracy (100 %) in both datasets in the virtual default mode network (DMN) source space.

Undifferentiated versus retinoic acid - differentiated SH-SY5Y cells in investigation of markers of neural function in toxicological research

The SH-SY5Y human neuroblastoma cell line is a standard in vitro experimental model of neuronal-like cells used in neuroscience and toxicological research. These cells can be differentiated into mature neurons, most commonly using retinoic acid (RA). Despite differences in characteristics, both undifferentiated and differentiated SH-SY5Y cells are used in research. However, due to uncertainties regarding the expression of specific markers of neural function in each culture, there is no definite conclusion on which culture is better suited for (neuro)toxicological and/or neuroscience investigations. To address this dilemma, we investigated the basal expression/activity of the key elements of acetylcholine, dopamine, serotonin and GABA neurotransmitter pathways, along with the elements involved in exocytosis of neurotransmitters, and neuron electrophysiological activity in undifferentiated and in RA–differentiated SH-SY5Y cells using a 6-day differentiation protocol. Our findings revealed that both SH-SY5Y cell types are functionally active. While undifferentiated SH-SY5Y cells exhibited greater multipotency in the expression of tested markers, most of those markers expressed in both cell types showed higher expression levels in RA-differentiated SH-SY5Y cells. Our results suggest that the 6-day differentiation protocol with RA induces maturation, but not differentiation of the cells into specific neuron phenotype. The greater multipotency of undifferentiated cells in neural markers expression, together with their higher sensitivity to xenobiotic exposure and more simple cultivation protocols, make them a better candidate for high throughput toxicological screenings. Differentiated neurons are better suited for neuroscience researches that require higher expression of more specific neural markers and the specific types of neural cells.

Effects of 2 Hz flickering light on refractive state, fundus imaging and visual function of C57BL/6 mice

In this study, we investigated the effects of flickering light on refractive development of mice and the changes of fundus structure and function during this process. C57BL/6 mice were randomly divided into control group and flickering light-induced myopia (FLM) group. Mice in the control group were fed under normal lighting. FLM group mice were fed under lighting with a duty cycle of 50% and flash frequency of 2 Hz. Refractive status, axial length (AL), corneal radius of curvature (CRC), and electroretinogram signals were measured in all animals before treatment and at 2 and 4 weeks after treatment. Retinal thickness (RT), choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). After 4 weeks of flickering light stimulation, the mice became myopia, the AL increased, but the CRC remained constant. The induction of myopia reduced the implicit time and amplitude of a-wave and b-wave in electroretinogram, which affects the function of retina. Full-layer retinal thickness, ChT and ChBP decreased at both 2 and 4 weeks after flickering light induction. The superficial and middle layers of the retina were significantly thinner, while the deep layer was only slightly thinner without statistical significance. Calculated by the concentric circle algorithm, the decrease of choroidal blood perfusion in FLM was mainly concentrated in the concentric circle area with the optic disc as the center radius of 150-450μm. In conclusion, the present study shows that flickering light can successfully induce myopia in C57BL/6 mice, affect the electrophysiological activity of retina, and cause changes in fundus tissue structure and blood flow.

Female-Biased Odorant Receptor MmedOR48 in the Parasitoid Microplitis mediator Broadly Tunes to Plant Volatiles.

Odorant receptors (ORs) play a crucial role in insect chemoreception. Here, a female-biased odorant receptor MmedOR48 in parasitoid Microplitis mediator was fully functionally characterized. The qPCR analysis suggested that the expression level of MmedOR48 increased significantly after adult emergence and was expressed much more in the antennae. Moreover, an in situ hybridization assay showed MmedOR48 was extensively located in the olfactory sensory neurons. In two-electrode voltage clamp recordings, recombinant MmedOR48 was broadly tuned to 23 kinds of volatiles, among which five plant aldehyde volatiles excited the strongest current recording values. Subsequent molecular docking analysis coupled with site-directed mutagenesis demonstrated that key amino acid residues Thr142, Gln80, Gln282, and Thr312 together formed the binding site in the active pocket for the typical aldehyde ligands. Furthermore, ligands of MmedOR48 could stimulate electrophysiological activities in female adults of the M. mediator. The main aldehyde ligand, nonanal, aroused significant behavioral preference of M. mediator in females than in males. These findings suggest that MmedOR48 may be involved in the recognition of plant volatiles in M. mediator, which provides valuable insight into understanding the olfactory mechanisms of parasitoids.

CXCL10 Enhances Acid-Sensing Ion Channel Currents in Rat Dorsal Root.

Both CXCL10/CXCR3 and acid-sensing ion channels (ASICs) are expressed in nociceptive sensory neurons and participate in various pain processes, but it is still unclear whether there is a link between them. Herein, we report that CXCL10 enhances the electrophysiological activity of ASICs in rat dorsal root ganglia (DRG) neurons. A brief (10min) application of CXCL10 increased acid-evoked ASIC currents in a concentration-dependent manner. CXCL10 increased the maximum response of ASICs to acidic stimuli without changing their sensitivity. CXCL10 enhanced ASIC currents in DRG cells through CXCR3, as this enhancement was completely blocked by AMG487, a selective CXCR3 antagonist. CXCL10 also increased ASIC3 currents in CHO cells coexpressing ASIC3 and CXCR3 but not in cells expressing ASIC3 alone. The CXCL10-mediated increase in ASIC currents was prevented by the application of either the G protein inhibitor GDP-β-S or the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 but not by the ERK inhibitor U0126 or the JNK inhibitor SP600125. Moreover, CXCL10 increased the number of action potentials triggered by acidic stimuli via CXCR3. CXCL10 dose-dependently exacerbated acid-induced nociceptive behavior in rats through peripheral CXCR3. These results indicated that CXCL10/CXCR3 signaling enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats via a p38 MAPK-dependent pathway, revealing a novel mechanism underlying pain. CXCL10/CXCR3 signaling may be an effective target in the treatment of pain associated with tissue acidification.

Learning a Hand Model from Dynamic Movements Using High-Density EMG and Convolutional Neural Networks.

Surface electromyography (sEMG) can sense the motor commands transmitted to the muscles. This work presents a deep learning method that can decode the electrophysiological activity of the forearm muscles into the movements of the human hand. We have recorded the kinematics and kinetics of the hand during a wide range of grasps and individual digit movements that cover 22 degrees of freedom of the hand at slow (0.5 Hz) and comfortable (1.5 Hz) movement speeds in 13 healthy participants. The input of the model consists of 320 non-invasive EMG sensors placed on the extrinsic hand muscles. Our network achieves accurate continuous estimation of both kinematics and kinetics, surpassing the performance of comparable networks reported in the literature. By examining the latent space of the network, we find evidence that it mapped EMG activity into the anatomy of the hand at the individual digit level. In contrast to what is observed from the low-pass filtered EMG and linear decoding approaches, we found that the full-bandwidth EMG (monopolar unfiltered) signals during synergistic and individual digit movements contain distinct neural embeddings that encode each movement of the human hand. These manifolds consistently represent the anatomy of the hand and are generalized across participants. Moreover, we found a task-specific distribution of the embeddings without any presence of correlated activations during multi- and individual-digit tasks. The proposed method could advance the control of assistive hand devices by providing a robust and intuitive interface between muscle signals and hand movements.

Electrophysiological correlation of auditory selective spatial attention in the "cocktail party" situation.

The auditory system can selectively attend to the target source in complex environments, the phenomenon known as the "cocktail party" effect. However, the spatiotemporal dynamics of electrophysiological activity associated with auditory selective spatial attention (ASSA) remain largely unexplored. In this study, single-source and multiple-source paradigms were designed to simulate different auditory environments, and microstate analysis was introduced to reveal the electrophysiological correlates of ASSA. Furthermore, cortical source analysis was employed to reveal the neural activity regions of these microstates. The results showed that five microstates could explain the spatiotemporal dynamics of ASSA, ranging from MS1 to MS5. Notably, MS2 and MS3 showed significantly lower partial properties in multiple-source situations than in single-source situations, whereas MS4 had shorter durations and MS5 longer durations in multiple-source situations than in single-source situations. MS1 had insignificant differences between the two situations. Cortical source analysis showed that the activation regions of these microstates initially transferred from the right temporal cortex to the temporal-parietal cortex, and subsequently to the dorsofrontal cortex. Moreover, the neural activity of the single-source situations was greater than that of the multiple-source situations in MS2 and MS3, correlating with the N1 and P2 components, with the greatest differences observed in the superior temporal gyrus and inferior parietal lobule. These findings suggest that these specific microstates and their associated activation regions may serve as promising substrates for decoding ASSA in complex environments.

Structural and theoretical basis for drug development targeting TMEM16A: Inhibition mechanism of tracheloside analogs

Ion channels play a crucial role in the electrophysiological activities of organisms. The calcium-activated chloride channel TMEM16A is involved in various physiological processes. Therefore, inhibitors of TMEM16A are used to treat diseases caused by TMEM16A dysfunction. However, the unclear inhibition mechanism hinders the progress of drug development. Based on our previous study, we found that the molecular structures of TMEM16A inhibitors tracheloside, matairesinoside and arctigenin are similar. In this study, we conducted a structure-based virtual screening of tracheloside analogs from the PubChem database. The six tracheloside analogs with the highest affinity to TMEM16A were selected, and their inhibitory effects were detected by fluorescence and electrophysiological experiments. Subsequently, the interaction between the tracheloside analogs and TMEM16A was investigated through molecular docking and site-directed mutagenesis. Based on the above results, the mechanism of inhibition of TMEM16A gated conformation by tracheloside analogs was proposed. These findings provide a structural and theoretical basis for drug development targeting TMEM16A.

Preparatory activity of anterior insula predicts conflict errors: integrating convolutional neural networks and neural mass models

Preparatory brain activity is a cornerstone of proactive cognitive control, a top-down process optimizing attention, perception, and inhibition, fostering cognitive flexibility and adaptive attention control in the human brain. In this study, we proposed a neuroimaging-informed convolutional neural network model to predict cognitive control performance from the baseline pre-stimulus preparatory electrophysiological activity of core cognitive control regions. Particularly, combined with perturbation-based occlusion sensitivity analysis, we pinpointed regions with the most predictive preparatory activity for proactive cognitive control. We found that preparatory arrhythmic broadband neural dynamics in the right anterior insula, right precentral gyrus, and the right opercular part of inferior frontal gyrus (posterior ventrolateral prefrontal cortex), are highly predictive of prospective cognitive control performance. The pre-stimulus preparatory activity in these regions corresponds to readiness for conflict detection, inhibitory control, and overall elaborate attentional processing. We integrated the convolutional neural network with biologically inspired Jansen-Rit neural mass model to investigate neurostimulation effects on cognitive control. High-frequency stimulation (130 Hz) of the left anterior insula provides significant cognitive enhancement, especially in reducing conflict errors, despite the right anterior insula’s higher predictive value for prospective cognitive control performance. Thus, effective neurostimulation targets may differ from regions showing biomarker activity. Finally, we validated our theoretical finding by evaluating intrinsic neuromodulation through neurofeedback-guided volitional control in an independent dataset. We found that left anterior insula was intrinsically modulated in real-time by volitional control of emotional valence, but not arousal. Our findings further highlight central role of anterior insula in orchestrating proactive cognitive control processes, positioning it at the top of hierarchy for cognitive control.

Structural and sequential regularities modulate phrase-rate neural tracking

Electrophysiological brain activity has been shown to synchronize with the quasi-regular repetition of grammatical phrases in connected speech—so-called phrase-rate neural tracking. Current debate centers around whether this phenomenon is best explained in terms of the syntactic properties of phrases or in terms of syntax-external information, such as the sequential repetition of parts of speech. As these two factors were confounded in previous studies, much of the literature is compatible with both accounts. Here, we used electroencephalography (EEG) to determine if and when the brain is sensitive to both types of information. Twenty native speakers of Mandarin Chinese listened to isochronously presented streams of monosyllabic words, which contained either grammatical two-word phrases (e.g., catch fish, sell house) or non-grammatical word combinations (e.g., full lend, bread far). Within the grammatical conditions, we varied two structural factors: the position of the head of each phrase and the type of attachment. Within the non-grammatical conditions, we varied the consistency with which parts of speech were repeated. Tracking was quantified through evoked power and inter-trial phase coherence, both derived from the frequency-domain representation of EEG responses. As expected, neural tracking at the phrase rate was stronger in grammatical sequences than in non-grammatical sequences without syntactic structure. Moreover, it was modulated by both attachment type and head position, revealing the structure-sensitivity of phrase-rate tracking. We additionally found that the brain tracks the repetition of parts of speech in non-grammatical sequences. These data provide an integrative perspective on the current debate about neural tracking effects, revealing that the brain utilizes regularities computed over multiple levels of linguistic representation in guiding rhythmic computation.

Electrophysiological activity pattern of mouse hippocampal CA1 and dentate gyrus under isoflurane anesthesia

General anesthesia can impact a patient’s memory and cognition by influencing hippocampal function. The CA1 and dentate gyrus (DG), serving as the primary efferent and gateway of the hippocampal trisynaptic circuit facilitating cognitive learning and memory functions, exhibit significant differences in cellular composition, molecular makeup, and responses to various stimuli. However, the effects of isoflurane-induced general anesthesia on CA1 and DG neuronal activity in mice are not well understood. In this study, utilizing electrophysiological recordings, we examined neuronal population dynamics and single-unit activity (SUA) of CA1 and DG in freely behaving mice during natural sleep and general anesthesia. Our findings reveal that isoflurane anesthesia shifts local field potential (LFP) to delta frequency and reduces the firing rate of SUA in both CA1 and DG, compared to wakefulness. Additionally, the firing rates of DG neurons are significantly lower than CA1 neurons during isoflurane anesthesia, and the recovery of theta power is slower in DG than in CA1 during the transition from anesthesia to wakefulness, indicating a stronger and more prolonged impact of isoflurane anesthesia on DG. This work presents a suitable approach for studying brain activities during general anesthesia and provides evidence for distinct effects of isoflurane anesthesia on hippocampal subregions.

Astrocytes facilitate gabazine-evoked electrophysiological hyperactivity and distinct biochemical responses in mature neuronal cultures.

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult brain that binds to GABA receptors and hyperpolarizes the postsynaptic neuron. Gabazine acts as a competitive antagonist to type A GABA receptors (GABAAR), thereby causing diminished neuronal hyperpolarization and GABAAR-mediated inhibition. However, the biochemical effects and the potential regulatory role of astrocytes in this process remain poorly understood. To address this, we investigated the neuronal responses of gabazine in rat cortical cultures containing varying ratios of neurons and astrocytes. Electrophysiological characterization was performed utilizing microelectrode arrays (MEAs) with topologically controlled microcircuit cultures that enabled control of neuronal network growth. Biochemical analysis of the cultures was performed using traditional dissociated cultures on coverslips. Our study indicates that, upon gabazine stimulation, astrocyte-rich neuronal cultures exhibit elevated electrophysiological activity and tyrosine phosphorylation of tropomyosin receptor kinase B (TrkB; receptor for brain-derived neurotrophic factor), along with distinct cytokine secretion profiles. Notably, neurons lacking proper astrocytic support were found to experience synapse loss and decreased mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, astrocytes contributed to neuronal viability, morphology, vascular endothelial growth factor (VEGF) secretion, and overall neuronal network functionality, highlighting the multifunctional role of astrocytes.

Electric field temporal interference stimulation of neurons in vitro.

Electrical stimulation (ES) techniques, such as deep brain and transcranial electrical stimulation, have shown promise in alleviating the symptoms of depression and other neurological disorders in vivo. A new noninvasive ES method called temporal interference stimulation (TIS), possesses great potential as it can be used to steer the stimulation and possibly selectively modulate different brain regions. To study TIS in a controlled environment, we successfully established an in vitro 'TIS on a chip' setup using rat cortical neurons on microelectrode arrays (MEAs) in combination with a current stimulator. We validated the developed TIS system and demonstrated the spatial steerability of the stimulation by direct electric field measurements in the chip setup. We stimulated cultures of rat cortical neurons at 28 days in vitro (DIV) by two-channel stimulation delivering 1) TIS at 653 Hz and 643 Hz, resulting in a 10 Hz frequency envelope, 2) low-frequency stimulation (LFS) at 10 Hz and 3) high-frequency stimulation (HFS) at 653 Hz. Unstimulated cultures were used as control/sham. We observed the differences in the electric field strengths during TIS, HFS, and LFS. Moreover, HFS and LFS had the smallest effects on neuronal activity. Instead, TIS elicited neuronal electrophysiological responses, especially 24 hours after stimulation. Our 'TIS on a chip' approach eludicates the applicability of TIS as a method to modulate neuronal electrophysiological activity. The TIS on a chip approach provides spatially steerable stimuli while mitigating the effects of high stimulus fields near the stimulation electrodes. Thus, the approach opens new avenues for stimulation on a chip applications, allowing the study of neuronal responses to gain insights into the potential clinical applications of TIS in treating various brain disorders.

Classifying Neuronal Cell Types Based on Shared Electrophysiological Information from Humans and Mice.

The brain is an intricate system that controls a variety of functions. It consists of a vast number of cells that exhibit diverse characteristics. To understand brain function in health and disease, it is crucial to classify neurons accurately. Recent advancements in machine learning have provided a way to classify neurons based on their electrophysiological activity. This paper presents a deep-learning framework that classifies neurons solely on this basis. The framework uses data from the Allen Cell Types database, which contains a survey of biological features derived from single-cell recordings from mice and humans. The shared information from both sources is used to classify neurons into their broad types with the help of a joint model. An accurate domain-adaptive model, integrating electrophysiological data from both mice and humans, is implemented. Furthermore, data from mouse neurons, which also includes labels of transgenic mouse lines, is further classified into subtypes using an interpretable neural network model. The framework provides state-of-the-art results in terms of accuracy and precision while also providing explanations for the predictions.

Silicon Optrode with a Micromirror‐Tip Providing Tunable Beam Profile During Infrared Neuromodulation of the Rat Neocortex

AbstractInfrared (IR) neuromodulation holds an increasing potential in brain research, which is fueled by novel neuroengineering approaches facilitating the exploration of the biophysical mechanism in the microscale. The group lays down the fundamentals of spatially controlled optical manipulation of inherently temperature‐sensitive neuronal populations. The concept and in vivo validation of a multifunctional, optical stimulation microdevice is presented, which expands the capabilities of conventional optrodes by coupling IR light through a monolithically integrated parabolic micromirror. Heat distribution in the irradiated volume is experimentally analyzed, and the performance of the integrated electrophysiological recording components of the device is tested in the neocortex of anesthetized rodents. Evoked single‐cell responses upon IR irradiation through the novel microtool are evaluated in multiple trials. The safe operation of the implanted device is also presented using immunohistological methods. The results confirm that shift in temperature distribution in the vicinity of the optrode tip can be controlled by the integrated photonic components, and in parallel with the optical stimulation, the device is suitable to interrogate the evoked electrophysiological activity at the single neuron level. The customizable and scalable optrode system provides a new pathway to tailor the location of the heat maximum during infrared neural stimulation.

A Female-Biased Chemosensory Protein PxutCSP19 in the Antennae of Papilio xuthus Tuned to Host Volatiles and Insecticides.

Chemosensory protein (CSP) genes significantly enriched in the female antennae are potential molecular candidates for mediating female oviposition behaviors. In this study, we presented the interaction mechanisms of a female-antenna-biased PxutCSP19 in Papilio xuthus to 47 host volatiles, four biopesticides and 24 synthetic insecticides. Using a bioinformatics-based homology search, 22 genes orthologous to PxutCSP19 were identified from 22 other Papilio butterflies with high sequence identities to each other (73.20~98.72%). Multiple alignment analyses revealed a particularly extended N-terminus of Papilio CSP19s (an average of 154 residues) compared to insects' typical CSPs (approximately 120 residues). The expression profiles indicated that PxutCSP19 was significantly enriched in the female antennae, with a 31.81-fold difference relative to the male antennae. In ligand-binding assays, PxutCSP19 could strongly bind six host odorants with high affinities, ranging from dissociation constant (Ki) values of 20.44 ± 0.64 μM to 22.71 ± 0.73 μM. Notably, this protein was tuned to a monoterpenoid alcohol, linalool, which generally existed in the Rutaceae plants and elicited electrophysiological and behavioral activities of the swallowtail butterfly. On the other hand, PxutCSP19 was also capable of binding eight insecticides with stronger binding abilities (Ki < 12 μM) compared to host odorants. When an extended N-terminal region of PxutCSP19 was truncated into two different proteins, they did not significantly affect the binding of PxutCSP19 to ligands with high affinities, suggesting that this extended N-terminal sequences were not involved in the specificity of ligand recognition. Altogether, our study sheds light on the putative roles of PxutCSP19 enriched in the female antennae of P. xuthus in the perception of host volatiles and the sequestering of insecticides, and it complements the knowledge of butterfly CSPs in olfaction and insecticide resistance.

Human Cervical Epidural Spinal Electrogram Topographically Maps Distinct Volitional Movements.

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of 5 human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4-8 Hz) band, feature increased theta-gamma phase-amplitude coupling, and that this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements.Significance statement The electrophysiology of the human spinal cord remains incompletely characterized. We build on our previous work in describing a novel method of recording spinal epidural electrograms from awake human participants by showing that SEGs (spinal electrograms) recorded from the cervical spinal cord during volitional upper extremity movements demonstrate spectral changes time-locked to movement that feature prominent increase in theta band power, theta-gamma phase-amplitude coupling, and are well delineated from pre-movement baseline. These spectral changes can also be topographically mapped to the cervical spine in a myotome distribution broadly consistent with maps generated from intraoperative stimulation studies in humans and direct stimulation experiments in monkeys. Our methodology may aid in the developing spatiotemporal maps for neurostimulation protocols to recapitulate naturalistic movements.

The involvement of the piriform cortex in non-lesional temporal lobe epilepsy: an uncommon component of the epileptogenic network.

The piriform cortex is recognized as highly epileptogenic in rodents, yet its electrophysiological role in human epilepsy remains understudied. Recent surgical outcomes have suggested potential benefits in resecting the piriform cortex for cases of medial temporal lobe epilepsy. However, little is known about its electrophysiological activity in human epilepsy. This case-series study aimed to explore the electrophysiological role of the piriform cortex within the epileptogenic network among patients with suspected temporal lobe epilepsy. Participants were recruited from Emory University Hospital or Children's Healthcare of Atlanta, with non-lesional frontotemporal or temporal lobe hypotheses, undergoing stereoelectroencephalographic studies. Specifically, focus was placed on patients with one or more electrode contacts in the piriform cortex. Primary objectives included determining piriform cortex involvement within the electrophysiologically defined epileptogenic network and assessing the effects of electrical stimulation. Twenty-two patients were included in the study. Notably, only one patient exhibited piriform cortex involvement at seizure onset, associated with an olfactory aura. Two patients showed early piriform cortex involvement, while others displayed late or no involvement. Electrical stimulation of the piriform cortex induced after-discharges in three patients and replicated a habitual seizure in one. These findings present a contrast to surgical outcome studies, suggesting that the piriform cortex may not typically play a significant role in the epileptogenic network among patients with non-lesional temporal lobe epilepsy.

Dissociating prosodic from syntactic delta activity during natural speech comprehension.

Decoding human speech requires the brain to segment the incoming acoustic signal into meaningful linguistic units, ranging from syllables and words to phrases. Integrating these linguistic constituents into a coherent percept sets the root of compositional meaning and hence understanding. One important cue for segmentation in natural speech is prosodic cues, such as pauses, but their interplay with higher-level linguistic processing is still unknown. Here, we dissociate the neural tracking of prosodic pauses from the segmentation of multi-word chunks using magnetoencephalography (MEG). We find that manipulating the regularity of pauses disrupts slow speech-brain tracking bilaterally in auditory areas (below 2Hz) and in turn increases left-lateralized coherence of higher-frequency auditory activity at speech onsets (around 25-45Hz). Critically, we also find that multi-word chunks-defined as short, coherent bundles of inter-word dependencies-are processed through the rhythmic fluctuations of low-frequency activity (below 2Hz) bilaterally and independently of prosodic cues. Importantly, low-frequency alignment at chunk onsets increases the accuracy of an encoding model in bilateral auditory and frontal areas while controlling for the effect of acoustics. Our findings provide novel insights into the neural basis of speech perception, demonstrating that both acoustic features (prosodic cues) and abstract linguistic processing at the multi-word timescale are underpinned independently by low-frequency electrophysiological brain activity in the delta frequency range.

Electrophysiological Activity of Multifunctional and Behaviorally Specialized Spinal Neurons Involved in Swimming, Scratching, and Flexion Reflex in Turtles.

The adult turtle spinal cord can generate multiple kinds of limb movements, including swimming, three forms of scratching, and limb withdrawal (flexion reflex), even without brain input and sensory feedback. There are many multifunctional spinal neurons, activated during multiple motor patterns, and some behaviorally specialized neurons, activated during only one. How do multifunctional and behaviorally specialized neurons each contribute to motor output? We analyzed in vivo intracellular recordings of multifunctional and specialized neurons. Neurons tended to spike in the same phase of the hip-flexor (HF) activity cycle during swimming and scratching, though one preferred opposite phases. During both swimming and scratching, a larger fraction of multifunctional neurons than specialized neurons were highly rhythmic. One group of multifunctional neurons was active during the HF-on phase and another during the HF-off phase. Thus, HF-extensor alternation may be generated by a subset of multifunctional spinal neurons during both swimming and scratching. Scratch-specialized neurons and flexion reflex-selective neurons may instead trigger their respective motor patterns, by biasing activity of multifunctional neurons. In phase-averaged membrane potentials of multifunctional neurons, trough phases were more highly correlated between swimming and scratching than peak phases, suggesting that rhythmic inhibition plays a greater role than rhythmic excitation. We also provide the first intracellular recording of a turtle swim-specialized neuron: tonically excited during swimming but inactive during scratching and flexion reflex. It displayed an excitatory postsynaptic potential following each swim-evoking electrical stimulus and thus may be an intermediary between reticulospinal axons and the swimming CPG they activate.